The goal of this research project is to provide information as to the causes of accelerated atherosclerosis and increased thickening of capillary basement membranes is diabetes mellitus. Specifically, two early events in the development of atherosclerosis, smooth muscle cell proliferation and collagen synthesis, will be studied both in vivo using diabetic rabbits fed cholesterol to induce atherosclerosis and in vitro utilizing cultures of vascular smooth muscle cells. Smooth muscle cell proliferation will be examined in vivo by radioautography of incorporated tritiated thymidine into the smooth muscle cells of the coronary and renal arteries and the thoracic and abdominal aorta. Collagen synthesis and deposition will be investigated in arteries by immunofluorescent antibody staining to determine the relative synthesis and deposition of type I and III collagens. For our in vitro studies cultures of vascular smooth muscle cells will be established from diabetic and nondiabetic rabbits and humans to study the effects of glucose, insulin, growth hormone and diabetic serum on cell proliferation and collagen synthesis by these cells. Also, vascular endothelial cells will be cultured to study basement membrane collagen production in these cell when grown under conditions approximating those found in the diabetic state.